Taste disorders, including taste distortion and taste loss, are associated with diseases, aging, and medications and contribute significantly to anorexia, malnutrition, and depression. Despite recent progress in identifying taste receptors and taste signaling proteins, little is known about the underlying mechanisms of taste disorders. Our long-term objective is to elucidate the molecular and cellular basis of gustatory dysfunction. Several lines of evidence suggest that inflammation is an important contributing factor to the pathogenesis of taste disorders. First, taste abnormality is frequently associated with inflammatory conditions, such as infections and autoimmune diseases. Second, inflammatory stimuli can change taste preference and food intake. Third, taste bud cells express receptors and signaling molecules for inflammatory factors. Fourth, we have shown that inflammatory cytokines, such as interferons, can alter gene expression and induce cell death in taste buds. So far, however, how inflammation affects taste sensation remains largely unknown. In this application, we propose to study the mechanisms of inflammation-induced taste disorders in animal models. We are going to pursue the following specific aims: 1) We will study the effects of acute and chronic inflammation on taste bud cell renewal and turnover. 2) We will determine the roles of cytokines in mediating the effects of inflammation on taste bud cell renewal and turnover. 3) We will investigate the effects of inflammation and cytokines on taste function. Results from these studies will be important for understanding the roles of inflammation in taste disorders, which will be useful for developing new treatment strategies. In addition, this research will further our knowledge on the regulatory mechanisms of taste bud cell turnover. PUBLIC HEALTH RELEVANCE: Our research investigates the mechanisms of taste dysfunction, a condition associated with aging, various diseases, and some medications. This research is critical for developing new strategies to prevent and treat such disorders.